The chemical pathogenesis of Leigh's disease is being investigated. All documented patients wth Leigh's disease have a deficiency of thiamine triphosphate (TTP) in brain, and a factor in their body fluids which specifically inhibits the cerebral enzyme synthesizing TTP. The basic purpose of this research project is to describe specific characteristics of the inhibiting factor. Both the inhibitor and the inhibited enzyme will be purifed to the extent that their interaction can be studied, and the kinetics of the reactiondetermined. Utilizing the talents of the basic science departments pure inhibitor will be prepared and its composition determined. Additional amounts of inhibitor will be used in an attempt to prepare specific antibody for the inhibitor. If the latter is available the assay for this inhibitor will be vastly simplified, and become available to numerous laboratories in thi country. In additon we will be studying a cat with a genetic neurodegeneration, associated with a deficiency of total hexosaminidase, and storage of Gm2 ganglioside in brain. The long term goal of this latter aspect is to indicate methods of enzyme replacement in the human gangliosidoses. BIBLIOGRAPHIC REFERENCES: Murphy, J.V., and Craig, L.J : Leigh's disease, significance of the biochemical changes in brain. J. Neurology, Neurosurgery and Psychiatry, 38:1100-1103, 1975. Murphy, J.V., Craig, L.H., Diven, W.J. and Matta E.J.: Diagosis of Leigh's Disease Utilizing Cultured Fibroblasts, submitted to Archives of Neurology, 1975.